an-isolated-working-heart-system-for-large-animal-models

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Duke University Medical Center

The effect of exercise training on myocardial Na(+)/H(+) exchanger-1 (NHE1) protein expression was examined. Adult female Sprague-Dawley rats were randomly divided into sedentary (S; n = 8) and exercised (E; n = 9) groups. Twenty-four hours after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Heart weight and heart weight/body weight from E rats was significantly increased by 7.1 and 7.2 % (P < 0.05), respectively, compared with S hearts. The E hearts displayed 15 % greater cardiac output and 35 % external cardiac work compared with the S group at both low and high workloads (P < 0.05 for both parameters). Left ventricular tissue from the same hearts was homogenized and NHE1 and Na(+)/Ca(2+) exchanger (NCX) content determined by Western blotting. E hearts had a 38 % (P < 0.001) reduction in NHE1 content related to S hearts, and there was no difference in NCX content between groups. Cytochrome c oxidase activity in plantaris increased by 100 % (P < 0.05) and was assessed as a marker of mitochondria content and to verify training status. Our data indicate that exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE1 content in heart.

Myocardial Na+/H+ exchanger-1 (NHE1) content is decreased by exercise training.

The myocardial Na(+)/H(+) exchanger-1 (NHE1) plays a major role in regulation of intracellular pH, and its upregulation has been implicated in increased ischemia-reperfusion injury and other pathologies. Hydrogen peroxide (H2O2) increases NHE1 activity acutely via ERK1/2 signaling. Chronic strenuous exercise upregulates NHE1 in skeletal muscle, but we hypothesize this will not occur in the heart, because exercise creates a cardioprotective phenotype. NHE1 activity and its regulation by H2O2 were examined at physiological pH using isolated cardiomyocytes from female Sprague-Dawley rats exercised on a treadmill for 5 wk (E; n = 11). Compared with sedentary (S; n = 15), E displayed increases (P < 0.05) in heart-to-body weight ratio (6.8%) and plantaris mitochondria content (89%). NHE1 activity (acid efflux rate following an acid load) was 209% greater in E (0.65 ± 0.12 vs. 2.01 ± 0.29 fmol/min). The difference was attributed primarily to greater cell volume (22.2 ± 0.6 vs. 34.3 ± 1.1 pl) and intracellular pH-buffering capacity (33.94 ± 1.59 vs. 65.82 ± 5.20 mM/pH unit) of E myocytes. H2O2 stimulation (100 μM) raised NHE1 activity significantly less in E (45%) than S (167%); however, activity remained 185% greater in E. ERK1/2 inhibition abrogated the increases. H2O2-stimulated ERK1/2 phosphorylation levels normalized to total ERK1/2 were similar between groups. Content of NHE1 and activities of H2O2 scavengers were also similar. We observed that intracellular pH-buffering capacity differences between groups became progressively less with declining pH, which may be an exercise-induced cardioprotective adaptation to lower NHE1 activity during certain pathological situations. We conclude that strenuous endurance exercise increases myocardial NHE1 activity at physiological pH, which would likely enhance cardiac performance under physiological conditions.

Bryan J. Feger

Department of Surgery

Duke University Medical Center

An Isolated Working Heart System for Large Animal Models

Bryan J. Feger

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Surgery

Duke University Medical Center

An Isolated Working Heart System for Large Animal Models

Department of Surgery